Imaging mass spectrometry is receiving broad attention as a technique for detecting the distribution of substances within a sample, in the field of pathological studies, drug development, and so on. Typically, in mass spectrometry, a sample is irradiated with a laser beam, an ion beam, an electron beam, or the like so as to be ionized, and the resulting ions are separated in accordance with their mass-to-charge ratios. Thus, a spectrum of detected intensities as a function of the mass-to-charge ratio is obtained. In imaging mass spectrometry, a surface of an object to be measured (sample) is subjected to mass spectrometry two-dimensionally, and a two-dimensional distribution of detected intensities of the substances corresponding to the respective mass-to-charge ratios is obtained. Thus, information on the distribution of the substances at the surface of the sample is obtained. Imaging mass spectrometry enables biomolecules, such as protein, and drug molecules to be identified, and also makes it possible to measure the spatial distribution of such biomolecules and drug molecules at high spatial resolution.
A charged particle beam, such as a laser beam and an ion beam, is used in order to ionize a sample, and such a beam is generally referred to as a primary beam. In addition, an ion generated when an ion beam is used as a primary beam (primary ion beam) is referred to as a secondary ion, and a technique for detecting such secondary ions is known as secondary-ion mass spectrometry (SIMS). Furthermore, matrix-assisted laser desorption/ionization (MALDI) is a known example in which a laser beam is used as a primary beam, and a sample that has been crystallized by being mixed into a matrix is irradiated with a pulsed laser beam so as to be ionized.
A time-of-flight technique, which is suitable for detecting molecules having large mass, such as protein, is often employed for detecting an ionized sample by separating the ionized sample in accordance with the mass-to-charge ratio. In a time-of-flight mass spectrometry apparatus, ions are generated in pulses at a surface of a sample, and accelerated through an electric field; or ions are accelerated in pulses through an electric field in vacuum. Ions travel at different flight speeds in accordance with their mass-to-charge ratios, and thus the mass-to-charge ratio of a given ion can be determined by measuring the time (i.e., time of flight) it takes for the given ion to travel a predetermined distance to reach a detector after being emitted from the sample.
In addition, imaging mass spectrometry includes scanning imaging mass spectrometry and projection-type imaging mass spectrometry.
In scanning imaging mass spectrometry, small regions (the size is dependent on the beam diameter of a primary beam) on a sample are successively subjected to mass spectrometry, and the distribution of substances is reconstructed from the result of the mass spectrometry and the positional information of the small regions. Thus, the spatial resolution is determined by the beam diameter of the primary beam and the positional precision of the scanning primary beam.
In projection-type imaging mass spectrometry, a sample is irradiated with a primary beam so as to be ionized, and a position- and time-sensitive detector detects the time at which a generated ion has reached the detector and the position on the detection surface of the detector which the ion has reached. Furthermore, a projection-type charged particle optical system configured to form an image of the ion on the detector is provided, and thus the mass of the detected ion and the position of the ion on the surface of the sample are detected simultaneously. Accordingly, the spatial distribution of substances contained in the sample can be obtained. The projection-type charged particle optical system is formed by an electrostatic lens, a magnetic lens, or the like.
An electrostatic lens is often used as a projection-type charged particle optical system (PTL1). An electrostatic lens causes ions to converge through an electric field and forms an image of the ions on a detector. The spatial resolution of a projection-type charged particle optical system is determined by the accuracy in determining the positions on the detection surface where the ions have reached (positional resolution), the magnification or the aberration of the charged particle optical system, and so forth.
In the field of pathological studies or drug development, a minute structure in the order of microns needs to be observed when a cell or a microstructure is to be observed. In the meantime, a broader range in the order of millimeters or centimeters needs to be observed when a biological tissue is to be observed. Therefore, it is effective to switch the magnification in such a manner that, in the case of the former, the measurement is carried out in a condition in which the spatial resolution is high (high magnification), and in the case of the latter, the measurement is carried out in a condition in which the spatial resolution is low but the measurement range is broad (low magnification).